Efficacy and Safety of Rapid Intermittent Compared With Slow Continuous Correction in Severe Hyponatremia Patients

Seoul National University Hospital178 enrolled

Overview

This study will investigate efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patient with moderately severe or severe symptomatic severe hyponatremia

Moderate to severe symptomatic hyponatremia requires prompt treatment with hypertonic saline. The extent and rate of increase in serum sodium (sNa) levels during treatment are critical. Several methods for continuous infusion of hypertonic saline were used to guide rate of fluid administered to achieve the required serum sodium target. As based on static model, they had a bias to over-correction of hyponatremia. Alternative approach to treatment with hypertonic fluid is to use small, fixed boluses to achieve controlled increments in sNa. However, there was no high quality evidence on whether hypertonic saline are best given in continuous infusion (preferred by most) or bolus injection. The aim of present study, a multi-center (Seoul National University Bundang Hospital \[2016.8\~\], Seoul National University Boramae Medical Center \[2016. 9\~\], Hallym University Dongtan Sacred Heart Hospital \[2017.7\~\]), randomized, open labelled, controlled clinical trial, is to investigate efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patient with moderately severe or severe symptomatic severe hyponatremia. A total 178 patients, who suffer from symptomatic severe hyponatremia, will be enrolled and randomly assigned to receive either intermittent bolus infusion or slow continuous infusion by 3% hypertonic saline. Subjects will take different rate of 3% hypertonic saline for 24-48 hours stratified by severity of clinical symptoms. Serum sodium will be measured at every six hours during two days.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

178

Conditions

Hyponatremia Symptomatic

Interventions

3% hypertonic salineDRUG

The same as above

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * In emergency setting (2016.6-) and/or inpatients at ward (2018.9-) * Glucose corrected serum sodium ≤125 mmol/L * Patients with moderately severe or severe symptom * Moderately severe :Nausea without vomiting Drowsy, Headache General weakness, myalgia * Severe :Vomiting, Stupor, Seizures, Coma (Glasgow Coma Scale ≤8) * written consent Exclusion Criteria: * Pseudohyponatremia: serum osmolality \> 275 mOsm/kg \- If the serum osmolality is \> 275 mOsm/kg but the BUN is ≥ 30 mg/dL, the patients can be registered if calculated serum osmolality (2 x plasma \[Na\] + \[Glucose\]/18) is \<275 mOsm/kg * Primary polydipsia: urine osmolality ≤ 100 mOsm/kg * Glucose corrected serum sodium \>125 mmol/L * Arterial hypotension (SBP \<90mmHg and MAP \<70mmHg) * Anuria or urinary outlet obstruction * Liver disease * transaminase levels \>3 times the upper limit normal * Known LC with ascites or diuretics use or PSE Hx or Varix Hx * Uncontrolled diabetes mellitus (HbA1C \> 9%) * Women who are pregnant or breast feeding * History of cardiac surgery excluding PCA, acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, acute coronary syndrome, cebrovascular trauma, and increased intracranial pressure within the 3 months prior to randomization

Locations (3)

Hallym University Dongtan Sacred Hospital

Hwaseong-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital Clinical Trial Center

Seongnam-si, Gyeonggi-do, South Korea

Seoul National University Boramae Hospital

Seoul, South Korea

Outcomes

Primary Outcomes

Incidence of overcorrection rate at any given period

Increase in sNa by \>12 mmol/L within 24 hours or Increase in sNa by \>18 mmol/L within 48 hours All subjects receive hypertonic saline by intermittent bolus or slow continuous infusion for 48 hours, serum Na will be measured.

Time frame: up to 48 hours

Secondary Outcomes

Rapid improvement of symptoms

Change of symptoms from baseline to 24 hours after hypertonic fluid treatment

Time frame: up to 24 hours

Time from treatment initiation to an increase of serum Na ≥ 5 mmol/L

Time frame: up to 48 hours

Incidence of target correction rate

Target correction rate is defined by achieved serum Na \<10 mmol/L within 24 hours, achieved serum Na \<18 mmol/L within 48 hours

Time frame: up to 48 hours

Time to serum Na >130 mmol/L

Time from treatment initiation to achieved serum Na\> 130mmol/L

Time frame: up to 48 hours

Length of hospital stay

Time frame: up to 8 weeks

Incidence of additional treatment

Additional treatment is performed if symptom is not relieved or undercorrection develops (achieved Na \< 5mmol/L with 24 hours or achieved Na \<12mmol/L within 48 hours)

Time frame: up to 48 hours

Incidence of osmotic demyelinating syndrome confirmed by ICD -10 code or MRI

Time frame: up to 48 hours

Data from ClinicalTrials.gov

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